Myelin has been considered to be metabolically inert. This view on the stability of myelin has been recently disputed. It is suggested that the apparent stability of myelin may be due to reutilization of the injected precursor. Experiments are planned to reinvestigate the metabolism of myelin. Various precursors of phospholipids, cerebrosides and sulphatides will be injected intraventricularly into brains of young and adult rats. The turnover rates of these lipids in the purified myelin and microsomes, as well as of water soluble intermediate precursors of these lipids in brain, will be simultaneously determined. It is expected that the turnover rates of the water soluble precursors will determine the contribution due to reutilization of the precursors for the synthesis of lipids. Various studies have indicated that the site of these lipids synthesis is the endoplasmic reticulum (microsomes). It is not yet known where myelin lipids are formed. They could be synthesized by myelin in situ or could be transported to myelin from the synthetic site. Both these alternatives will be examined. In vitro studies should determine the biosynthetic capacity of myelin for either de novo synthesis or "partial" synthesis. This will be done by assaying the enzyme CDP-choline or -ethanolamine:1,2 diglyceride choline- or ethanolamine-phosphotransferase and by studying the acylation of lysophosphoglycerides. Studies will be carried out to determine if an exchange or transfer of lipids between microsomes and myelin occurs. Pulse-chase experiments with isolated oligodendroglia cells are designed to determine if such an exchange is possible in the cells having cellular integrity. Studies on the isolation of myelin or "myelin-like" membranes from Quaking animals and turnover of such membranes are planned.